jy231(jy231) injection for the treatment of relapsed or refractory b cell lymphoma/ leukemia

Conditions: B-ALL; B-NHL

Summary: this study is an investigator-initiated single center, single arm clinical study with a target population of patients with relapsed or refractory b cell lymphoma / leukemia. it is an early exploratory clinical study of the safety, tolerability and initial efficacy of jy231 injection in the treatment of relapsed or refractory b cell lymphoma / leukemia.

this open-label, single-arm study is designed to evaluate the efficacy and safety of in vivo car-t cell therapy in patients with relapsed refractory b-cell lymphoma/leukaemia. upon enrolment, leukapheresis will be performed and patients will receive 3-5 days of fludarabine and cyclophosphamide lymphodepleting therapy followed by an intravenous infusion of the jy231 preparation. following the infusion, subjects will be evaluated for safety and efficacy for up to 3 months. for subjects who achieve durable remission after 3 months of infusion, follow-up will be conducted for at least 24 months to determine if the disease is under control.

Eligibility criteria:
inclusion criteria: 1. subject voluntarily sign informed consent and are willing and able to comply with all trial requirements; 2. age is 18-75 years old and gender is not limited; 3. malignancy cells in bone marrow or peripheral blood are cluster of differentiation 19 - positive(cd19+) detected by flow cytometric analysis; 4. meet the clinical criteria for relapsed or refractory b-cell lymphoma, including: indolent lymphoma (inhl), such as follicular lymphoma (fl) and marginal zone lymphoma (mzl); aggressive b-cell lymphoma, like diffuse large b-cell lymphoma (dlbcl), primary mediastinal large b-cell lymphoma (pmbcl), transformed follicular lymphoma (tfl), and t-rich lymphocyte-bearing large b-cell lymphoma (tcrbcl), or have a diagnosis of acute b-lymphocytic leukemia (b-all) and meet one of the following conditions: * refractory b-all: those who did not achieve complete remission after 2 courses of standard induction regimen chemotherapy, or those who did not achieve complete remission after first-line or multi-line salvage chemotherapy; * relapsed b-all: relapse within 12 months after first remission, or relapse after first-line / multi-line salvage chemotherapy; * relapse after autologous or allogeneic hematopoietic stem cell transplantation; in addition, patients with philadelphia chromosome positive (ph +) should be relapsed after at least two tyrosine kinase inhibitors (tki) treatment, or they could not tolerate tki therapy, or have a t315i mutation, resistant to tki drugs. 5. morphological examination of bone marrow cells showed the proportion of primitive and naive lymphocytes was\> 5%; 6. no hematopoietic stem cell transplantation(hsct) within 6 months before enrollment; 7. at least one measurable lesion was imaging for relapsed or refractory b cell lymphoma, long diameter of\> 15mm, or extranodal lesion of\> 10mm, along with a positive positron emission tomography - computed tomography(pet-ct) examination. 8. more than 12 weeks of expected survival period 9. baseline eastern cooperative oncology group(ecog) score was 0-1; 10. adequate organ function (criteria regarding liver and kidney function can be moderately relaxed): * glutamic aminotransferase (alt) ≤3 times upper limit of normal (uln); * grass aminotransferase (ast) ≤3 times uln; * total bilirubin ≤1.5 times uln; * serum creatinine ≤ 1.5 times uln, or creatinine clearance ≥ 60 ml/min; * indoor oxygen saturation ≥ 92%; * left ventricular ejection fraction (lvef)≥55%, echocardiography confirmed no pericardial effusion and no clinically significant ecg findings; * there is no clinically significant pleural effusion; 11. adequate bone marrow reserve without transfusion, defined as: * absolute neutrophil count (anc)\>1.000 / mm3; * absolute lymphocyte count (alc)≥ 300 / mm3; * platelet≥50.000/mm3; * hemoglobin\>8.0 g/dl; 12. subjects using the following drugs need to meet the following conditions: * steroids: the therapeutic dose of steroids must be stopped 72 hours before jy231 infusion. however, physiological alternative doses of steroids are allowed; * immunosuppression: any immunosuppressive drug must be stopped at ≥4 weeks prior to enrollment; * antiproliferative therapy other than lymphodepletion chemotherapy within two weeks of infusion; * cluster of differentiation 20(cd20) antibody-related therapy must be stopped within 4 weeks before infusion or 5 half-lives after the cd20 antibody; * cns disease prophylaxis must be stopped 1 week before jy231 infusion (e. g. intrathecal methotrexate). 13. reproductive men, sexual partners ensure effective contraception; fertile women, adopted effective contraception and agreed to use contraception throughout the study period. exclusion criteria: 1. subjects with active cerebrospinal fluid malignant cells or brain metastases, or subjects with active central nervous system (cns) lymphoma, or cns leukaemia; 2. subjects with a history of active cns disease, such as seizures, cerebrovascular ischemia / hemorrhage, dementia, cerebellar disease, or any autoimmune disease associated with cns involvement; 3. subjects who have received other study drugs within 30 days before screening, or are still in the washout period; 4. patients who have previously received any anti-cd19 / anti-cluster of differentiation 3(cd3) therapy or any other anti-cd19 therapy (except for those with normal t cell numbers and function and with cd19-positive tumors); 5. patients who have been previously treated with any gene therapy product, including chimeric antigen receptor t(car-t) therapy (except patients who do not have car-t cells in vivo and have normal t cell number and function and are with cd19 positive tumors); 6. subjects with radiation therapy within 2 weeks prior to the infusion; 7. subjects with active hepatitis b (defined as hepatitis b virus(hbv) dna test value\> 500 iu / ml) or hepatitis c (hcv rna positive); subjects with hiv positive or treponema pallidum positive; 8. subjects with uncontrolled acute life-threatening bacterial, viral, or fungal infection (e. g. positive blood culture 72 hours before infusion); 9. subjects with unstable angina pectoris and / or myocardial infarction within the 6 months prior to screening; 10. subjects with concurrent or previously diagnosed with other malignancies, except for the patients under following conditions: * well treated basal cells, papillary thyroid carcinoma, squamous cell carcinoma (adequate wound healing is required before enrollment into this study); * carcinoma in situ of cervical cancer or breast cancer, after curative treatment, showed no signs of recurrence for at least 3 years before the study; * the primary malignancy has been completely removed and is in complete remission for 5 years. 11. arrhythmic subjects without medical management control; 12. subjects receiving oral anticoagulation within 1 week before jy231 injection infusion; 13. having active neurological autoimmune or inflammatory conditions (such as guillain-barre syndrome, amyotrophic lateral sclerosis); 14. female subjects in pregnant or lactating, or women with planned pregnancy within 2 years after jy231 infusion or male partner with planned pregnancy within 2 years after jy231 infusion; 15. subjects with taboo study procedures or other medical conditions that may put them at unacceptable risk according to the investigator's judgment and / or clinical criteria. 16. other conditions that the investigator believes that the subjects should not be enrolled in this clinical trial, such as poor compliance.